Real-World evidence revelations: The potential of patient support programmes to provide data on medication usage

Patient Support Programmes (PSPs) are used by the pharmaceutical industry to provide education and support to consumers to overcome the challenges they face managing their condition and treatment. Whilst there is an increasing number of PSPs, limited information is available on whether these programmes contribute to safety signals. PSPs do not have a scientific hypothesis, nor are they governed by a protocol. However, by their nature, PSPs inevitably generate adverse event (AE) reports. The main goal of the research was to gather all Novartis-initiated PSPs for sacubitril/valsartan, followed by research in the company safety database to identify all AE reports emanating from these PSPs. Core data sheets (CDS) were reviewed to assess if these PSPs contributed to any new, regulatory-authority approved, validated signals. Overall, AEs entered into the safety database from PSPs confirmed no contribution to CDS updates. Detailed review of real-world data revealed tablet splitting or taking one higher dose tablet a day instead of twice daily. This research, and subsequent analyses, revealed that PSPs did not impact safety label changes for sacubitril/valsartan. It revealed an important finding concerning drug utilisation i.e. splitting of sacubitril/valsartan tablets to reduce cost. This finding suggests that PSPs may contribute important real-world data on patterns of medication usage. There remains a paucity of literature available on this topic, hence further research is required to assess if it would be worth designing PSPs for collecting data on drug utilisation and (lack of) efficacy. Such information from PSPs could be important for all stakeholders.

supporting guidance in Good Vigilance Practice Module VI (EMA, 2017), better defines and governs these programmes.As defined, a PSP is an organised system where the marketing authorisation holder (MAH) receives and collects information relating to the use of its medicinal products.The programmes can be postauthorisation patient support and disease management programmes, surveys of patients and healthcare providers, information gathering on patient compliance, or compensation/ re-imbursement schemes.
Under GVP module VI, these programmes are considered solicited reports and the MAH is responsible for collecting and evaluating full and comprehensive case information in order to asses and report individual cases related to the studied (or supplied) medicinal product.The MAH should request causality assessment from the primary reporter of each case report, and where possible and consented an appropriate level of due diligence should be exercised by the MAH.
Since 2012, the governance of PSPs has evolved.However, the underlying question, whether such efforts from the MAH leads to any newly identified signals on the medicinal product, is still not clear.Limited evidence is available in the public domain (e.g.Portnoff JM et al. 2017;Jokinen JD et al. 2019), but more research is required to determine if there has been an impact of the 2012 PV legislation on patient safety.Indeed there is a bigger question concerning whether there have been any tangible public health benefits from the significant investment of time and resources applied by MAHs to govern and manage PSPs.GVP module VI and obliges the MAH to collect AEs deriving from such programmes.
However, there are no further guidance available and each MAH must determine how to ensure AE collection and reporting.The paper revealed that most companies reported "regular oversight" of PSPs and other organised data collection systems with few companies admitting lesser oversight.The question remains what a regular oversight is as it may be interpreted differently.
Neither of the papers however, analysed if such effort from the MAH on collecting and reporting AEs from PSPs in fact add any value to the actual signal detection process considering the fact that such programmes are not designed for AE collection.Currently at Novartis, there is a robust system in place with several global and local processes to ensure the appropriate management and oversight of PSPs.

Expected outcome
The expected outcome is that PSPs will not generate any signals as they are not intended to collect AEs and there are no written protocol or hypothesis to examine.
PSPs however, can be beneficial for reviewing the acceptance, adherence and tolerability and many more other aspects of participating patients and healthcare professionals.
Regulators should assess the time and effort spent by the MAH on collection and reporting of adverse events from PSPs in comparison to the benefit and information provided from these reports to ensure useful investment for case handling for public health reason.Does it really add value to identifying new signals or could resources be deployed in other much more useful methods?Regulators might need to reassess the process of individual case submission from PSPs to a more beneficial periodic report submission with focus on patient and health care professional experience.

Aims and Objectives (please list)
The aim of the research is to evaluate the evolution of PSPs within Novartis and further assess if the 2012 EU PV legislation supports the pharmacovigilance and signal detection of the medicinal products involved in PSPs.In general, PSPs do not need scientific hypothesis or governed by a protocol hence these programmes are not safety oriented.However, the nature of these programmes generate reportable AEs.The project will also review the benefit of collection and reporting of adverse events from PSPs in comparison to the time and effort spent by the MAH to fulfil the current regulations.
This review and assessment will be achieved by focusing on the wide range of PSPs in association with two Novartis innovative medicines, Cosentyx (secukinumab) and Entresto (Sacubitril/valsartan); and the development of their safety profile.
The justification for the selection of Cosentyx and Entresto is that the Novartis publication policy supports the release of additional information in the public domain after a defined period.
Cosentyx was first registered in Japan on 24 th Dec 2014 (International Birth Date or IBD).It was approved by the European Medicines Agency (EMA) on 14 th January 2015, followed by the US Food and Drug Administration (FDA) on 21 st January 2015.
To date Novartis has obtained approvals in 92 countries worldwide Cosentyx is registered to treat moderate to severe plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and pustular psoriasis (in Japan only).The formulation of Cosentyx is a pen or prefilled syringe containing 150 mg of secukinumab for subcutaneous administration.
Entresto was first approved and registered in the United States of America (USA) on 7 th Jul 2015 (IBD), followed by the EMA approval on 25 th Sep 2015.Novartis is currently the MAH in 111 countries worldwide.Entresto is registered for the treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF) in adult patients.
Over the past five years, in the PSP database (POPsys) there are over a hundred PSPs on Cosentyx and over 70 on Entresto.This is likely to provide sufficient information for analysis.This time period is sufficient for Novartis to allow meaningful use of the data.
The two chosen products have very different profiles, e.g.indication, formulation, target group, therapy areas etc.However, both have been on the market roughly the same time.It would be interesting to see if PSPs have contributed to signals.
Additionally, the project will look deeper into the PSPs from the patient perspective.
Since patients can report adverse events via the support programmes there is a higher possibility to receive and collect patient tolerability information.Tolerability is a preference whereby the patient is able to tolerate a certain level of AEs to continue treatment, e.g.non-serious patient reported tolerability of the product in comparison to unexpected adverse events.The project will further look into patient adherence to and acceptance of the product.
DocuSign Envelope ID: D8283142-F48D-49D3-952D-2CCE14EEDAA3 Jokinen et al. is the first multi-company collaborative effort using statistical methods to analyse the different sources of safety data i.e. solicited and spontaneous reports combined for signal detection.The conclusion was that the increased volumes of safety data from PSPs do not necessarily correlate with improved safety signal detection.The paper also suggests an over 400% increase in AE reporting in a decade due to PSPs, market research and social media programmes.None of these programmes are designed to collect AEs however; PSPs do generate a great number of AEs due to their nature.PSPs are structured to provide support in different forms of services, solutions or initiatives to assist patients in managing their disease or medication.This finding further strengthens the hypothesis and research question whether this reporting from PSPs leads to any validated signals that further strengthens knowledge of the safety profile of the medication.Portnoff et al. researched the governance and oversight of PSPs at the MAH level.PSPs fall under the scope of "Organized data collection systems" as classified by DocuSign Envelope ID: D8283142-F48D-49D3-952D-2CCE14EEDAA3